Why do people have withdrawal problems?

Most psychiatric drugs work on body chemicals called neurotransmitters, which carry messages between nerves, or between nerves and muscles, glands or other organs. They cross the gap (the synapse) between the nerve and its target. There are a lot of different neurotransmitters, and in the brain they interact and influence each other in subtle ways, which we have scarcely begun to understand. The main neurotransmitters, about which we know most, are dopamine, noradrenaline

The neurotransmitters work by interacting with receptors. These are minute areas on the nerve or other cells that make the cell respond in the appropriate way. Some psychiatric drugs block these receptors, reducing the effect of a neurotransmitter. Others increase the level of a neurotransmitter, so its effects last longer. Because they all interact, changing the level of one neurotransmitter will change others; so however well a drug is targeted towards a particular receptor, it will have a knock-on effect on the whole system.

One knock-on effect of many psychiatric drugs is to suppress acetylcholine, and this causes some of the side effects people experience. Using a drug can change the number of receptors people have, and this seems to be the cause of many withdrawal problems:

If a drug increases the levels of neurotransmitters at the synapse, then the number of receptors there reduces. This means the person may not have enough receptors after the drug is withdrawn, making them more likely to relapse. (SSRIs will raise the concentration of serotonin by inhibiting its reuptake.)

If a drug blocks the receptors, then new receptors are created to make up the shortfall. This makes the person extra sensitive to the neurotransmitter, so that when he or she comes off the drug, this ‘supersensitivity’ makes them more vulnerable to psychosis and at a high risk of suffering a relapse. (Antipsychotics block dopamine receptors.) Newer ‘atypical’ antipsychotic drugs are better targeted to particular dopamine receptors, but they still have serious side effects and should be limited to the lowest possible dose for the shortest possible time. A lot of people who have been ‘stuck’ for years on the older drugs might do better on the newer drugs, or might at least like to try.

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